The goals of this study are to determine if the withdrawal of sympathetic tone leads to greater blood flow to exercising muscle. We will also determine if this greater flow leads to less muscle acidosis and less sympathetic discharge. We will also determine if in subjects with heart failure, the effects of sympathetic withdrawal are greater than they are in age matched controls. We hypothesize that in heart failure, sympathetic blockade will increase limb flow, reduce muscle acidosis, and attenuate the muscle reflex response to exercise. During the last GCRC period, we have perfected the bretylium bier block procedure. We have studied the effect of this block on limb blood flow during forearm exercise sympathetic discharge, and muscle metabolism. Sympathetic blockade produced a two-fold increase in forearm blood flow and vascular conductance. (P<0.05) both at rest and during hand grip contractions. Hemoglobin saturation was increased 30% at rest following sympathetic blockade but was not different from the control trial during contractions. Similarly, exercise venous plasma lactate, potassium and hydrogen ion concentration were not different following sympathetic blockade. Separate nuclear magnetiic resonance studies indicated that intracellular acidosis was not affected by sympathetic blockade. The data suggest that forearm oxygen uptake and lactate production were both increased two-fold during the bretylium trial.